10-29683621-A-G

Variant names:

• chr10-29683621-A-G
• rs11007696
• ENST00000375400.7:c.-301+2932T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001323599.2(SVIL):​c.-301+2932T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,082 control chromosomes in the GnomAD database, including 8,983 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (8983 hom., cov: 32)
• Consequence: SVIL NM_001323599.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.42

Genes affected

SVIL (HGNC:11480): (supervillin) This gene encodes a bipartite protein with distinct amino- and carboxy-terminal domains. The amino-terminus contains nuclear localization signals and the carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. The gene product is tightly associated with both actin filaments and plasma membranes, suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. The encoded protein appears to aid in both myosin II assembly during cell spreading and disassembly of focal adhesions. Several transcript variants encoding different isoforms of supervillin have been described. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SVIL	NM_001323599.2	c.-301+2932T>C		intron_variant	Intron 2 of 38		NP_001310528.1
SVIL	NM_001323600.1	c.-301+2932T>C		intron_variant	Intron 2 of 36		NP_001310529.1
SVIL	NM_003174.3	c.-301+2932T>C		intron_variant	Intron 2 of 35		NP_003165.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SVIL	ENST00000375400.7	c.-301+2932T>C		intron_variant	Intron 2 of 35	1		ENSP00000364549.3
SVIL	ENST00000674475.1	c.-301+2932T>C		intron_variant	Intron 2 of 38			ENSP00000501521.1
SVIL	ENST00000674490.1	c.-301+2932T>C		intron_variant	Intron 2 of 5			ENSP00000501398.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51714 AN: 151964 Hom.: 8973 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.216

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.320

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.340 AC: 51765 AN: 152082 Hom.: 8983 Cov.: 32 AF XY: 0.343 AC XY: 25519 AN XY: 74326

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.307

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.323

Alfa AF: 0.319 Hom.: 10803

Bravo AF: 0.342

Asia WGS AF: 0.418 AC: 1455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.2
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11007696; hg19: chr10-29972550;